Hypotension due to postural alteration occurs commonly in the elderly, usually as a result of inadequate cardioacceleration and/or insufficient peripheral vasoconstriction. The high morbidity associated with this disorder has contributed to a growing interest in cardiovascular homeostasis in the aged. The present proposal aims to systematically evaluate therat as a model for age-related changes in human cardiovascular response to physiological stimuli and to delineate the mechanisms underlying these changes, placing special emphasis on the effect of age on the afferent limb of the cardioacceleratory and baroreceptor reflex arc, an area in which no prior aging studies have been conducted. Specific aims include measurements of: 1. the effect of age on heart rate and blood pressure changes in response to (i) temporary restraint, (ii) postural change, (iii) hypoxia and hypercapnia, (iv) controlled hemorrhage, and (v) peripheral vasodilation; 2. the influence of age on intrinsic heart rate and short term modulators of heart rate variability; 3. effect of age on afferent neural activity at the following heart rate regulatory sites: (i) carotid baroreceptor, (ii) aortic baroreceptor, and (iii) atrial mechanoreceptor; 4. age-related changes in the sensitivity of the carotid and aortic baroreceptors; 5. effect of age on ionic sensitivity of the carotid baroreceptor; and 6. changes in the sympathetic modulation of carotid baroreceptor afferent activity with advancing age. Methodology: Adult (6 months) and senescent (24 months) rats will be studied in the intact anesthetized (unanesthetized in some of the first series of experiments) state in the experiments. Long-term Objectives: These proposed studies represent a direct extension of the applicant's currnent research on the effect of age on cardioacceleratory reflex mechanisms. The studies are of particular gerontologic interest because of the high prevalence of hypotension and its associated complications in the elderly. A systematic characterization of the age-related alterations in cardiovascular homeostatic reflexes and elucidation of their underlying mechanisms will likely facilitate the design and implementation of more appropriate modes of therapy for these deficits.